Individualized treatment decision-making is one of the most important challenges of medicine. To this end several studies have associated clinical variables or gene-expression profile with disease outcome, thereby providing help for clinicians making treatment decisions in several diseases (e.g. Hodgkin's disease, lymphoma).
In the last decade, treatment of rheumatoid arthritis (RA) has evolved to earlier and more aggressive treatment with disease-modifying antirheumatic drugs (DMARDs), as this therapeutic approach prevents joint damage and functional disability.
Patients that present to the outpatient clinic with a recent-onset arthritis are referred to as having early arthritis. Some of these patients may, at first presentation, have a disease that can be classified according to current arthritis evaluation criteria. For example, patients may be directly diagnosed with rheumatoid arthritis or reactive arthritis. Reactive arthritis is an acute form of arthritis which occurs after a viral or bacterial infection that spontaneously disappears in several weeks or months, and which features the following three conditions: (1) inflamed joints; (2) inflammation of the eyes (conjunctivitis); and (3) inflammation of the genital, urinary or gastrointestinal system. However, in rheumatologic practice, many patients present with an early arthritis that cannot be directly classified, and are considered to have an undifferentiated arthritis (UA) which is defined as an early arthritis for which, according to the available classification criteria, no diagnosis can be made.
When patients at first presentation are diagnosed with RA or reactive arthritis, prediction of whether the disease will become persistent or erosive is straightforward, as most RA patients will have a persistent and erosive disease course, while most patients with reactive arthritis will have a self-limiting disease course which in most cases, does not recur.
Several inception cohort studies have shown that about 40-50% of UA patients remit spontaneously, while one third develop RA. Treatment with methotrexate in patients with UA is known to inhibit progression to RA and inhibit joint damage. However, because of the potential toxicity associated with methotrexate and other DMARDs, only patients who have a high risk of developing RA, not those who are likely to remit spontaneously, should be treated with these agents. Thus, a method for predicting which patients with UA are most likely to develop RA would be exceedingly beneficial since only those most likely to develop RA would be exposed to potentially toxic therapeutic agents.
Morel and Combe (2005, Best Practice & Research Clinical Rheumatology 19:137-146) reviewed factors associated with the development of RA, or associated with the development of erosions in patients already diagnosed with the disease. This reference does not disclose a predictive model capable of assessing whether a patient with UA will develop RA.
In addition, several prognostic models that allow prediction of arthritis outcome have been described (e.g. Visser et al., 2002, Arthritis Rheum. 46:357-365; Visser, 2005, Best Practice & Research Clinical Rheumatology 19:55-72). However, the cohorts used to build and validate the models were made up of all early arthritis patients, including those with classified diagnoses (e.g., RA and reactive arthritis), as well as those with UA, with the objective of determining disease progression (erosive disease in particular), rather than differentiating RA from UA. Thus, these models are not capable of assisting in the differential diagnosis of patients that present with UA, and cannot be used to predict development of RA in patients with UA. Thus, there is a need for a method predicting whether patients with UA will develop RA that will address the deficiencies of previous models, as they do not have this predictive ability.